Extracellular Histones Promote Pulmonary Fibrosis in Patients With Coal Workers’ Pneumoconiosis

Abstract

This investigation assessed the profibrotic role that extracellular histones play in the pathogenesis of coal workers' pneumoconiosis (CWP). The correlation of extracellular histones with small opacity profusion (SOP) and transforming growth factor-β (TGF-β) was analyzed. The stimulating effect of extracellular histones on pulmonary fibroblast was assessed in vitro. The levels of extracellular histones in plasma were positively correlated with SOP and TGF-β in the coal miners investigated. Plasma collected from patients with CWP caused apparent lung fibroblast proliferation, while anti-H4 antibody antagonized the stimulating effect of the patient plasma by blocking histone H4. In vitro experiments showed that extracellular histones directly stimulated fibroblast proliferation. Consistent with our hypothesis, the concentrations of extracellular histones were indices of the severity of pulmonary fibrosis in simple CWP, and extracellular histones-targeted intervention could inhibit the proliferation of lung fibroblast.